Peptides derived from tumor epitopes are known to generate peptide-specific cytotoxic T cell responses. Tumor-associated carbohydrate antigens linked to immunogenic carrier proteins or in multimeric forms are used for antibody production, e.g., targeting B cell responses. The concept of a pan-cancer vaccine has been attractive for preventive use in normal healthy individuals and use post surgery or post chemo/radiation to minimize metastasis or limit further metastasis. Tumor Associated Carbohydrate Antigens (TACA) antigens as Thomsen-Friedenreich (TF) (Gal beta (β) 1-3GalNAc alpha (α) 1-R) and Tn (TF precursor, GalNAc alpha (α) 1-R) antigens have been used in a variety of formulation for the generation of specific antibodies in cancer patients. Traditional approaches have not been very successful in part because of the difficulties of manufacturing the requisite peptide derivatives and isolating the adjuvant proteins.
TF and Tn are expressed by mucins encoded in humans by the MUC1 gene. TF and Tn are precursors of the MN blood group substance expressed on glycophorin, which is also expressed on MUC1 found on tumor cells.
The productive development of memory CD8+ cytotoxic T cells (CTL) against tumors primarily depends on the strength of the antigenic stimuli, a consequence of the binding affinity of tumor antigens to class I molecules of the major histocompatibility complex (MHC), and the affinity of T cell receptors (TcRs) to MHC/peptide complexes. The homing and route of immunization also play an important role in determining the size of the initial CTL burst, depending on the participation of other immune cells that provide chemokines/lymphokines and co-stimulatory stimuli. Two big limitations in designing T cell-based immunotherapy against tumors are the characterization of immunogenic tumor epitopes and the frequent “self” nature of tumor antigens that leads to immunological tolerance.